The proposal involves the study of NADPH-cytochrome c (cytochrome P-450) reductase and its role in the electron transport systems concerned with the hydroxylation of drugs, carcinogens, steroids, and fatty acids. Experimental goals include: 1) studies on the liver and kidney microsomal omega- and omega-1)-hydroxylation of laurate with special emphasis on the role of various electron transport components in both NADH- and NADPH-mediated hydroxylation as well as effects of dietary manipulation on such systems; 2) studies on the mechanism of NADPH-cytochrome c (cytochrome P-450) reductase, solubilized by both detergent and proteolytic methods from the microsomal membrane, specifically pertaining to the reduction of various electron acceptors including cytochrome(s) P-450; 3) continuation of the studies on selenium deficiency and its effect on specific microsomal hydroxylations; 4) studies on the membrane-bound NADPH-cytochrome P-450 reductase; and 5) continuation of the studies on the role of NADPH-cytochrome c (cytochrome P-450) reductase in heme oxygenase catalyzed by liver and spleen microsomal constituents. BIBLIOGRAPHIC REFERENCES: "The Catalysis of Heme Degradation by Purified NADPH-Cytochrome c Reductase in the Absence of Other Microsomal Proteins", Masters, B.S.S., and Schacter, B.A. (l976) Ann. Clin. Research, in press. "Studies on Methemoglobin Reductase: Immunochemical Similarity of Soluble Methemoglobin Reductase and Cytochrome b5 of Human Erythrocytes with NADH-Cytochrome b5 Reductase and Cytochrome b5 of Rat Liver Microsomes", Kuma, F., Prough, R.A., and Masters, B.S.S. (1976) Arch. Biochem. Biophys., in press.